Figure 4

Myc functions as a hub gene of the BCR-operated transcriptional network to control life and death of B cells. (A) Steady-state mRNA levels of genes selected by two-way ANOVA (Table 2) in mature Myc^+/+ and Myc^Δ/Δ B cells treated with (BCR) or without (ctrl) anti-μ F(ab')₂. Each presented value is a normalized ratio of the expression level of each gene in BCR versus control sample for each genotype, i.e., Myc^+/+ and Myc^Δ/Δ. The data were normalized by dividing each ratio value by the wild-type BCR/ctrl ratio value for the corresponding gene. *, P < 0.05 (B) Myc-regulated transcriptional network controlling B-cell fate in response to BCR triggering. The candidate decision-making genes that were identified by the transcriptome analysis (Table 2) were associated with Myc according to the data (significance) presented in panel A. Genes were connected by dashed lines to indicate our indirect evidence for their interactions. Several genes (Wdr55, Spata13, Ptdss1, Rpo1-3, Hrb, Nola2, Idi1 and Ifrd1) were not connected to Myc because we did not observe any change in BCR/ctrl ratios when comparing both genotypes, i.e., Myc^+/+ and Myc^Δ/Δ. Genes in orange have been reported as neighbors of the Myc-network in B cells [37], and genes with a red underscore or genes whose names are written in blue have been described as direct Myc targets in [38] and [39], respectively.